____ ___________________________ _____________________ Hawaii Island Rat Lungworm Working Group Rat Lungworm IPM Daniel K. Inouye College of Pharmacy RLWL-10 University of Hawaii, Hilo Angiostrongyliasis - Rat Lungworm Disease Standards Addressed: Life Science MS-LS1-1. • Conduct an investigation to provide evidence that living things are made of cells; either one cell or many different numbers and types of cells. MS-LS1-2. • Develop and use a model to describe the function of a cell as a whole and ways parts of cells contribute to the function. MS-LS1-3. • Use argument supported by evidence for how the body is a system of interacting subsystems composed of groups of cells. Health Standard 1 Core Concepts: Understands concepts related to health promotion and disease prevention • HE 6-8. 1.9 Person Health and Wellness – Identify choices individuals can make to promote or harm their health. Standard 3: Self-management: Practice health enhancing behaviors and reduce health risks. • HE 6-8 3.2 Personal Health and Wellness – Explain the importance of assuming responsibility for personal health behaviors Standard 6 Decision making and goal setting: Decision making across topic areas • HE 6-8 6.1 Describe decision-making processes related to health-related decisions • HE 6-8 6.2 Access health-related decisions for consequences that affect oneself and others Standard 7: Advocacy: Advocate for personal family, and community health Advocacy across topic areas • HE 6-8 7.2 Use appropriate methods to communicate accurate health information and ideas 1 This lesson can be simplified for grades 5-6, modified for grades 7-8, and expanded upon for grades 9-12. Learning objectives: • Students will learn the medical term for rat lungworm disease. • Students will understand how the rat lungworm parasite travels through the host organism after ingestion of the parasite. • Students will understand how infection from rat lungworm disease can affect systems of the body. • Student will understand current diagnostic and treatments for rat lungworm disease. • Students will identify other diseases or injuries that can cause brain injury and how these are different or similar to angiostrongyliasis. Reading for understanding: Angiostrongyliasis Angiostrongyliasis is the medical term for rat lungworm disease. The term is associated with the scientific name of the parasite, Angiostrongylus cantonensis. Effects on the systems of the body The infective L3 stage larvae of the parasitic nematode Angiostrongylus cantonensis the rat lungworm will travel through the accidental host (human, dog, horse, primate, etc.) in a manner similar to the route it would take in the definitive host, the rat. Upon ingestion, the third stage A. cantonensis larvae safely travels through the stomach acid and enters the small intestine, both of which are part of the digestive system. The stomach, large intestine, small intestine, pancreas, liver, and gallbladder are all organs that make up the digestive system. Once in the small intestine, the larvae will burrow through the intestine wall. How the larvae get through the intestine wall is not known, they may chew their way through or they may excrete chemicals that aid them. Once through the intestine wall, the larvae enter blood vessels in the circulatory system of the host. This system is comprised of vein, arteries, and capillaries, and the blood is pumped throughout the body by the heart. The rat lungworm larvae use the blood stream like rivers to move through the body. Some of the larvae will pass through the lungs, which are part of the respiratory system, and then travel through the heart on their way to the brain, 2 which is part of the central nervous system. The larvae must reach the brain if they are to continue their development and become adults. The larvae that make it to the brain may travel to different parts of the brain, including the brain stem, which is communicates with the brain and the rest of the body and controls breathing, heart rate, blood pressure, consciousness, and sleep cycles, and the cerebellum, which coordinates voluntary movements including speech, posture, balance, and coordination. Some larvae may enter the cerebral cortex, which is the large part of the brain and is associated with higher functions such as thought and action. The larvae might also travel to the optic nerve, which is the nerve that connects the eye to the brain. As soon as larvae enter host they begin to feed on the host and grow. From microscopic examination of third stage larvae found in the lungs of rats we assume they are feeding on blood as their digestive tract is dark in color. You can see one of these larva in the photo on the left. Some of these larvae may remain in the lungs, however some are successful in their journey to their target, the central nervous system. Once a third stage (L3) larva arrives in the central nervous system it will grow through two molts, first becoming a fourth stage larva (L4) and then becoming a fifth stage larva (L5), or young adult rat lungworm. These larvae are now macroscopic, growing up to 15 millimeters in length. In the brain the larvae are feeding, burrowing, defecating, and damaging the myelin layer surrounding nerves. Myelin insulates nerves in a manner similar to the way the plastic coating on an electrical cord insulates the metal wires that transfer electricity. If the myelin coating is damaged the nerve signals cannot travel properly, which can cause bodily dis-function. Immune system response and inflammation Once the body detects these parasitic invaders, the immune system jumps into action. The rat lungworm is a fairly large parasite and even though it is still microscopic upon ingestion it is much bigger than bacterial or viral pathogens. The immune system will notice the presence of a large parasite in the body and 3 will produce a special, immune cell called an eosinophil. The eosinophil cells attack and kill A. cantonensis larvae, however the toxins that kill the parasites can also kill healthy brain cells and create inflammation in the brain. Because the brain is surrounded by the hard, bony skull, inflammation in the brain can be serious. Inflammation is one of the main symptoms that doctors will need to treat in cases of angiostrongyliasis, or rat lungworm disease. Disease Symptoms Angiostrongyliasis often presents with flu-like symptoms within days or several weeks after infection, although it is also stated that symptoms may occur months after infection. Initial symptoms can include issues associated with the digestive tract, including nausea and diarrhea. These symptoms may be caused by the passage of larvae through the intestinal wall and inflammation resulting from the damage. Victims then report feeling lethargic, having restlessness that may cause difficulty sleeping, a feeling of tingling or a crawling sensation under the skin, body and joint aches, and in some cases fever. These symptoms may possibly be experienced when the larvae are in the circulatory system. If the larvae reach their target of the central nervous system and brain, symptoms can become much more serious and include headache and a very stiff neck, which is a symptom of meningitis. Meningitis is a condition where the meninges, the tissues that surround the brain and spinal cord, become inflamed. Meningitis can be caused by bacteria, viruses, or in the case of rat lungworm, by a parasite. In cases caused by angiostrongyliasis, the meningitis is caused by the eosinophil cells the body produces to attack the rat lungworm parasite. While this cell it is good at killing the parasite, they can also damage nearby healthy tissue and may kill brain cells and create more inflammation. The meningitis caused by angiostrongyliasis is referred to as eosinophilic meningitis. This type of meningitis, unlike bacterial or viral meningitis, is not contagious, meaning it cannot be spread from person to person. If the disease continues to progress, even more serious symptoms may begin to occur. Bladder and bowel paralysis has been reported, requiring hospitalization of the victim. Extreme skin sensitivity known as paresthesia, is often reported by survivors of the disease. The skin becomes so sensitive that even the slightest breeze or touch of hair causes extreme pain. Headaches can become more severe and sensitivity to light may occur. There can be facial paralysis or paralysis of the lower limbs, memory loss, confusion, and hallucinations. The eyes may be affected 4 from damage to the retina, optic nerve, or nerves controlling muscles of the eye. Victims also may experience hearing loss. This is most likely the stage at which the larvae have reached fourth or fifth stage, or may be young adult rat lungworms, trying to find their way out of the brain. The damage caused by burrowing, feeding, defecating, and dying can cause significant and often irreversible damage, resulting in coma, death, or permanent disability. What we still don’t know It is generally assumed by the medical community that the young adult A. cantonensis cannot make their way out of the brain of a human. However, there are cases in young children where adult male and female A. cantonensis worms were found in the lungs of those who died of the disease. In Hawai'i, there are reports of lung complications from cases of rat lungworm disease. Could these problems be caused by adult worms finding their way out of the brain, or from third stage larvae that never made their way out of the lungs? There are many questions researchers have regarding this disease, as there are many victims who report on-going health problems, some of which change over time. Doctors have reported A. cantonensis can live for up to a year in the human host. If this is so, in what organs might they be lost and what damage might they causing? What we do know for sure is that rat lungworm disease in Hawai'i is a serious concern for public health and we all need to play a role in disease prevention.